The present invention relates to devices and methods for monitoring an analyte and, more particularly, to devices and methods for transdermal monitoring of an analyte.
The monitoring of certain analyte concentrations in the body enables early detection of health risks, and identifies the need for the introduction of therapeutic measures. One of the most commonly monitored analytes is glucose. The concentration of glucose in the blood is an important parameter which determines the appropriate dosages of insulin for diabetics. Various methods have been developed for monitoring glucose levels in the blood, including methods conducted in vivo. For example, an implantable fluorescence affinity hollow fiber sensor has been reported for the continuous transdermal monitoring of glucose in the blood (see, for example, Analytical Chemistry Vol. 72, No. 17, pp. 4185-4192). The interiors of such hollow fiber sensors are packed with cross-linked dextran beads and fluorescently-tagged bioreagents that display fluorescence changes with rising concentrations of glucose. Detection of the fluorescence is achieved extracorporeally (e.g., with an optical unit incorporating a laser and a photodetector) and is correlated with a concentration of glucose in the blood.
Unfortunately, the use of hollow fiber sensors for monitoring glucose in the blood suffers from a number of drawbacks. First, due to the narrow width of the fibers (ca. 200 microns) and the unpredictable ratio of dextran bead volume to void volume, reproducible packing of the interiors is extremely difficult, and leads to irreproducibility of fluorescence readings between fibers. Second, the narrow cross-section of the fibers results in weak fluorescence signals which are difficult to detect. Third, the fibers are delicate and prone to kinks, which complicates both the implantation and explantation of the fibers in the subcutaneous tissue. Fourth, the mobility of the cross-linked dextran beads in the fiber can result in the interposition of a bead between the excitation light from the laser and a fluorescently-tagged bioreagent, thus resulting in reduced signal.
The present invention is directed to overcoming these and other disadvantages inherent in hollow fiber sensors.
The scope of the present invention is defined solely by the appended claims, and is not affected to any degree by the statements within this summary.
Briefly stated, a device for monitoring an analyte embodying features of the present invention includes (a) a support having an interior surface and an exterior surface; (b) a substrate connected to the interior surface of the support, wherein the substrate is opaque; (c) a spacer connected to the interior surface of the support; (d) a labeled analogue, which binds reversibly to the substrate; and (e) a first membrane having an interior surface and an exterior surface, wherein the interior surface is connected to the spacer. The first membrane is permeable to the analyte and impermeable to the labeled analogue, and the first membrane is substantially transparent to each of an excitation wavelength and an emission wavelength of the fluorescent label. The dye absorbs a majority of the excitation and emission wavelengths of the fluorescent label. A chamber which encloses the substrate and the labeled analogue is defined by the interior surface of the support, the spacer, and the interior surface of the first membrane. The spacer exceeds the substrate in elevation such that a void volume exists between the interior surface of the first membrane and the substrate.
A method for monitoring an analyte embodying features of the present invention includes (a) implanting into a subcutaneous region of a patient a device in accordance with the present invention; (b) illuminating an extracutaneous region of the patient with a light having a wavelength which corresponds to the excitation wavelength of a fluorescently-labeled analogue contained in the device; (c) detecting a fluorescence signal corresponding to the emission wavelength of the fluorescently-labeled analogue using an extracutaneous photodetector; and (d) correlating the fluorescence signal with a concentration of the analyte.
The presently preferred embodiments described herein may possess one or more advantages relative to hollow fiber sensors, which can include but are but not limited to: higher fluorescence yields; reproducible introduction of bioreagents during manufacture of device; preservation of physical integrity of device during implantation and explantation; improved reproducible positioning of extracorporeal photodetector; significantly improved signal-to-noise ratio; and minimization of undesirable random fluorophore shadowing effects.